Development of a binding element, such as a receptor, ligand or an aptamer, in relatively short span of time remains a key challenge with regard to fine tuning of selectivity, sensitivity and specificity of the binding elements. Antibodies are valued for their high selectivity and affinity, however, the size and complex structure of antibodies may cause the molecules to be susceptible to degradation, aggregation, modification or denaturation. In addition, therapeutic application requires antibodies produced in mammalian cell lines; which is an expensive and complex process.
Engineered protein binders based on stable protein scaffolds have proved to be a successful strategy for production of affinity ligands since these ligands are smaller than antibodies, and are relatively stable and can be synthesized in microbial production systems. While many of these binders might be unsuitable for therapeutic applications because of their potential immunogenicity, they have found application as binders in analytical, diagnostics and chromatographic applications.
Binding-elements, such as aptamers are oligonucleotide affinity ligands that are selected for their high affinity binding to molecular targets. A variety of binding-elements have been developed based on nucleic acid, such as DNA and RNA. Binding-element discovery to date involves a selection process from a large library of DNA, RNA or modified nucleic acid oligomers involving multiple selection processes, such as SELEX (systematic evolution of ligands by exponential enrichment). Many rounds of selection and amplification are usually required to discover binding-elements with the desired affinity and selectivity. Thus the currently known process for selecting binding-elements are labor-intensive, time-consuming and expensive.
Therefore, there is a need to develop an alternative approach for discovery of binding-elements that provide adequate target affinity with increased specificity, while screening against molecules having structure similar to the target molecules.